Zontivity

08 mg to be taken once daily. 1). A delayed onset of action (at least 7 days) should be expected when starting therapy with Zontivity. There are limited data on the efficacy and safety of Zontivity beyond 24 months. 08 mg to be taken once daily.

For patients being started on Zontivity due to symptomatic PAD, therapy may be initiated at any time.

If a dose is missed:

A patient who misses a dose of Zontivity should skip the missed dose if it is within 12 hours of the next scheduled dose and take the next dose at the regular scheduled time. Coadministration with other antiplatelet medicinal products MI Patients taking Zontivity should also take acetylsalicylic acid with or without clopidogrel according to their indications or standard of care.

There is limited clinical experience with prasugrel and no experience with ticagrelor in the Phase 3 studies. Therefore, vorapaxar should not be used with prasugrel or ticagrelor. Vorapaxar should not be initiated in patients taking prasugrel or ticagrelor and in case of need for additional therapy with these agents, vorapaxar should be stopped.

PAD Patients taking Zontivity should also take acetylsalicylic acid or clopidogrel according to their indications or standard of care. 2). 2). However, reduced renal function is a risk factor for bleeding and should be considered before initiating Zontivity.

There is limited therapeutic experience in patients with severe renal impairment or end stage renal disease. Therefore, Zontivity should be used with caution in such patients. Hepatic impairment Reduced hepatic function is a risk factor for bleeding and should be considered before initiating Zontivity.

No dose adjustment is required in patients with mild hepatic impairment. Zontivity should be used with caution in patients with moderate hepatic impairment. 2). Paediatric population The safety and efficacy of Zontivity in children aged less than 18 years have not yet been established.

No data are available. Method of administration Oral use. The tablet may be taken with or without food.

Summary of the safety profile The most common adverse reaction reported during treatment is bleeding. Among the common bleeding events, epistaxis is the most frequent. Adverse reactions were evaluated in 19,632 patients treated with Zontivity [13,186 patients, including 2,187 patients treated for more than 3 years, in the TRA 2°P TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events) study and 6,446 patients in the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) study].

The adverse reactions of bleeding in Table 1 are summarized for the TRA 2°P TIMI 50 study. Non-bleeding adverse reactions in Table 1 are summarized for both the TRA 2°P TIMI 50 and TRACER studies. )Medicinal product no longer authorised 7 Tabulated list of Adverse Reactions Adverse reactions are classified according to frequency and System Organ Class.

Frequencies are defined as:

Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Table 1:

Tabulated List of Adverse Reactions System Organ Class Common Uncommon Blood and lymphatic system disorders Anaemia Eye disorders Conjunctival haemorrhage, diplopia Vascular disorders Haematoma Haemorrhage Respiratory, thoracic and mediastinal disorders Epistaxis Gastrointestinal disorders Gastritis, Gastrointestinal haemorrhage, Gingival bleeding, Melaena, Rectal haemorrhage Skin and subcutaneous tissue disorders Increased tendency to bruise Ecchymosis, Skin haemorrhage Renal and urinary disorders Haematuria Injury, poisoning, and procedural complications Contusion Wound haemorrhage Description of selected adverse reactions The adverse reactions in the vorapaxar-treated (n=10,059) and placebo-treated (n=10,049) post-MI or PAD patients with no history of stroke or TIA are shown below.

General risk of bleeding Zontivity increases the risk of bleeding, including ICH and sometimes fatal bleeding. 8). Zontivity increases the risk of bleeding in proportion to the patient’s underlying bleeding risk. , recent trauma, recent surgery, recent or recurrent gastrointestinal bleeding, or active peptic ulcer disease) should be considered before initiating Zontivity.

2)), low body weight, and reduced renal or hepatic function. In these subgroups, Zontivity should only be prescribed after careful assessment of individual potential risks and benefits and the need for co-medication that may further increase the risk of bleeding.

, anticoagulant and fibrinolytic therapy, and chronic nonsteroidal anti-inflammatory drugs (NSAIDS), selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors) may also increase the risk of bleeding in patients taking Zontivity.

There is limited experience with the concomitant use of vorapaxar with warfarin or other oral anticoagulants. The combination of vorapaxar with warfarin or other oral anticoagulants may increase the risk of bleeding and should be avoided.

In patients treated with vorapaxar the concomitant use of heparin (including low molecular weight heparin (LMWH)) might be associated with an increased risk of bleeding and caution is advised. Bleeding should be suspected in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), coronary artery bypass graft surgery (CABG), or other surgical procedures, even if the patient does not have any signs of bleeding.

Patients with low body weight (<60 kg) In general, a body weight <60 kg is a risk factor for bleeding. In TRA 2°P - TIMI 50, in vorapaxar- treated patients, including those with history of stroke, a higher rate of ICH was observed in patients weighing <60 kg compared to patients weighing ≥60 kg.

1).  Patients with a history of intracranial haemorrhage (ICH). 8). 4). Medicinal product no longer authorised 4